Transcription-dependent cytosine deamination is a novel mechanism in ultraviolet light-induced mutagenesis.

ABSTRACT: Skin cancer is the most ubiquitous cancer type in the Caucasian population, and its incidence is increasing rapidly [1]. Transcribed proliferation-related genes in dermal stem cells are targets for the induction of ultraviolet light (UV)-induced mutations that drive carcinogenesis. We have recently found that transcription of a gene increases its mutability by UV in mammalian stem cells, suggesting a role of transcription in skin carcinogenesis [2]. Here we show that transcription-associated UV-induced nucleotide substitutions are caused by increased deamination of cytosines to uracil within photolesions at the transcribed strand, presumably at sites of stalled transcription complexes. Additionally, via an independent mechanism, transcription of UV-damaged DNA induces the generation of int

SUBMITTER: Hendriks G 

PROVIDER: S-EPMC2818831 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature